|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2008-3-12
|
|
pubmed:abstractText |
Studies of mutations affecting lifespan in Caenorhabditis elegans show that mitochondrial generation of reactive oxygen species (ROS) plays a major causative role in organismal aging. Here, we describe a novel mechanism for regulating mitochondrial ROS production and lifespan in C. elegans: progressive mitochondrial protein modification by the glycolysis-derived dicarbonyl metabolite methylglyoxal (MG). We demonstrate that the activity of glyoxalase-1, an enzyme detoxifying MG, is markedly reduced with age despite unchanged levels of glyoxalase-1 mRNA. The decrease in enzymatic activity promotes accumulation of MG-derived adducts and oxidative stress markers, which cause further inhibition of glyoxalase-1 expression. Over-expression of the C. elegans glyoxalase-1 orthologue CeGly decreases MG modifications of mitochondrial proteins and mitochondrial ROS production, and prolongs C. elegans lifespan. In contrast, knock-down of CeGly increases MG modifications of mitochondrial proteins and mitochondrial ROS production, and decreases C. elegans lifespan.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
1474-9726
|
|
pubmed:author |
pubmed-author:AhmedNailaN,
pubmed-author:BaynesJohnJ,
pubmed-author:BeckerChristianC,
pubmed-author:BierhausAngelikaA,
pubmed-author:BozorgmehrFarastukF,
pubmed-author:BrownleeMichaelM,
pubmed-author:BuechlerMarkusM,
pubmed-author:DuXueliangX,
pubmed-author:El BakiRanda AbdRA,
pubmed-author:HamannAndreasA,
pubmed-author:HammesHans-PeterHP,
pubmed-author:HumpertPerP,
pubmed-author:HutterHaraldH,
pubmed-author:IbrahimYoussefY,
pubmed-author:KukudovGeorgiG,
pubmed-author:MiftariNexhatN,
pubmed-author:MoehrlenFrankF,
pubmed-author:MorcosMichaelM,
pubmed-author:NawrothPeter PPP,
pubmed-author:OikonomouDimitriosD,
pubmed-author:PfistererFriederikeF,
pubmed-author:SayedAhmed A RAA,
pubmed-author:SchlottererAndreasA,
pubmed-author:SchwengerVedatV,
pubmed-author:SternDavidD,
pubmed-author:ThornalleyPaulP,
pubmed-author:ThorpeSuzanneS,
pubmed-author:ZeierMartinM
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
7
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
260-9
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:18221415-Animals,
pubmed-meshheading:18221415-Caenorhabditis elegans,
pubmed-meshheading:18221415-Caenorhabditis elegans Proteins,
pubmed-meshheading:18221415-Enzyme Inhibitors,
pubmed-meshheading:18221415-Feedback, Physiological,
pubmed-meshheading:18221415-Gene Expression,
pubmed-meshheading:18221415-Lactoylglutathione Lyase,
pubmed-meshheading:18221415-Longevity,
pubmed-meshheading:18221415-Mitochondria,
pubmed-meshheading:18221415-Mitochondrial Proteins,
pubmed-meshheading:18221415-Mutation,
pubmed-meshheading:18221415-Oxidative Phosphorylation,
pubmed-meshheading:18221415-Oxidative Stress,
pubmed-meshheading:18221415-Protein Modification, Translational,
pubmed-meshheading:18221415-Pyruvaldehyde,
pubmed-meshheading:18221415-RNA, Helminth,
pubmed-meshheading:18221415-RNA, Messenger,
pubmed-meshheading:18221415-Reactive Oxygen Species
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans.
|
|
pubmed:affiliation |
Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
